4-88094705-C-T

Variant names:

• chr4-88094705-C-T
• rs2231164
• NM_004827.3:c.1738-46G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004827.3(ABCG2):​c.1738-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,483,750 control chromosomes in the GnomAD database, including 507,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (39400 hom., cov: 32)
  • Exomes 𝑓: 0.83 (467712 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 36 publications found

Genes affected

ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.1738-46G>A		intron_variant	Intron 14 of 15	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.1738-46G>A		intron_variant	Intron 14 of 15	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.1728-46G>A		intron_variant	Intron 14 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.1738-46G>A		intron_variant	Intron 15 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103076 AN: 152042 Hom.: 39407 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.751 AC: 185059 AN: 246320 AF XY: 0.774

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.532

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.799

GnomAD4 exome AF: 0.829 AC: 1104531 AN: 1331590 Hom.: 467712 Cov.: 20 AF XY: 0.832 AC XY: 557150 AN XY: 669684

African (AFR) AF: 0.300 AC: 9100 AN: 30366

American (AMR) AF: 0.537 AC: 23556 AN: 43894

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 22543 AN: 25230

East Asian (EAS) AF: 0.549 AC: 21361 AN: 38904

South Asian (SAS) AF: 0.796 AC: 65841 AN: 82754

European-Finnish (FIN) AF: 0.886 AC: 47186 AN: 53264

Middle Eastern (MID) AF: 0.831 AC: 4572 AN: 5502

European-Non Finnish (NFE) AF: 0.870 AC: 865977 AN: 995792

Other (OTH) AF: 0.794 AC: 44395 AN: 55884

GnomAD4 genome AF: 0.678 AC: 103091 AN: 152160 Hom.: 39400 Cov.: 32 AF XY: 0.679 AC XY: 50504 AN XY: 74398

African (AFR) AF: 0.318 AC: 13203 AN: 41472

American (AMR) AF: 0.629 AC: 9603 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3074 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5172

South Asian (SAS) AF: 0.774 AC: 3730 AN: 4820

European-Finnish (FIN) AF: 0.881 AC: 9354 AN: 10616

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.866 AC: 58924 AN: 68016

Other (OTH) AF: 0.711 AC: 1504 AN: 2114

Alfa AF: 0.771 Hom.: 102476

Bravo AF: 0.637

Asia WGS AF: 0.623 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2231164; hg19: chr4-89015857; COSMIC: COSV52945527;